Increased Disarray of Extracellular Matrix Collagen-I Fiber Network and Compromised Biomechanics in Aortae From...

Fibrillin‑1 (FBN1) mutations lead to extracellular matrix (ECM) defects with progressive aortic dilation in Marfan's syndrome (MFS). MFS thoracic aortas have increased stiffness, but how visco-elastic and microstructural abnormalities affect in vivo hemodynamics remains inconclusive. We applied ex vivo uniaxial visco-elasticity stress-relaxation testing and simultaneous 3D collagen Second Harmonic Generation (SHG) imaging to MFS and wt littermate linearized aortic strips with in vivo vascular function. MFS mouse (Fbn1^mgR/mgR) aortas were stiffer and more viscous. SHG imaging revealed MFS ECM disorganization at rest and stronger collagen-alignment strain response than wt strips, indicating greater fibrillar straightening capacity. in vivo, MFS mice developed early, progressive aortic dilation. Pulse wave velocity was elevated in young MFS mice pre-dilation but declined as aneurysms formed. Female MFS aortic peak pressure and velocity were normal, but reduced in MFS-males vs. wt. Ex vivo perfused wt carotid arteries were highly compliant. Female MFS carotids were stiffer, had reduced radial strain, a right‑shifted pressure-strain curve and minimal wall‑thickness changes. MFS carotids did not recover baseline diameter after perfusion, indicating impaired visco-elastic recoil. We demonstrate early visco-elastic MFS aortic dysfunction and ECM disorder. Mechanistically, the larger collagen-straightening capacity in MFS cannot compensate for the increased visco-elasticity during a beat-to-beat cycle.